Enhanced 3-Hydroxy-3-methyl-Glutaryl Coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor

Maria Gabriella Caruso, Maria Notarnicola, Mariarosaria Santillo, Aldo Cavallini, Alfredo Di Leo

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background: We have previously shown that 63.3% of colorectal cancer neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR. Materials and methods: the tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR activity was measured by radiochemical assay using 14C-HMG-CoA as substrate. Results: HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p = 0.02, Wilcoxon Rank sum test)]. Conclusions: the cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.

Original languageEnglish
Pages (from-to)451-454
Number of pages4
JournalAnticancer Research
Volume19
Issue number1 A
Publication statusPublished - 1999

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LDL Receptors
Human Activities
Colorectal Neoplasms
Oxidoreductases
Hydroxymethylglutaryl CoA Reductases
Nonparametric Statistics
glutaryl-coenzyme A
Cholesterol
Survival
Growth

Keywords

  • Colorectal carcinoma
  • HMG-CoA reductase
  • Low density lipoprotein receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Enhanced 3-Hydroxy-3-methyl-Glutaryl Coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor. / Caruso, Maria Gabriella; Notarnicola, Maria; Santillo, Mariarosaria; Cavallini, Aldo; Di Leo, Alfredo.

In: Anticancer Research, Vol. 19, No. 1 A, 1999, p. 451-454.

Research output: Contribution to journalArticle

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AU - Cavallini, Aldo

AU - Di Leo, Alfredo

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AB - Background: We have previously shown that 63.3% of colorectal cancer neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR. Materials and methods: the tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR activity was measured by radiochemical assay using 14C-HMG-CoA as substrate. Results: HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p = 0.02, Wilcoxon Rank sum test)]. Conclusions: the cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.

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